Abnormalities in red blood cell (RBC) cation permeability and cellular hydration are seen with many hemolytic disorders. The altered membrane physiology has been elucidated in a few of the disorders, but in virtually all cases, specific membrane structural abnormalities remain to be defined. Studies proposed here will further define the relationship between altered cation permeability, cellular hydration, and membrane protein-lipid interactions. These studies are divided into four parts. (1) Pathophysiology of RBC K-loss and cellular dehydration will be compared in RBCs from patients with hereditary hemolytic anemias (hereditary xerocytosis, pyruvate kinase deficiency), and several in vitro models. These studies will characterize membrane perturbations which modify K permeability, identify the physiologic effects of K and water loss, and evaluate changes in membrane protein-lipid organization. (2) Pathophysiology of increased Na and K permeability will be compared in RBCs from patients with hemolytic anemias (hereditary stomatocytosis, sickle cell anemia), Heinz body-containing RBCs, propranolol-treated cells, and RBCs with specific alteration in membrane proteins. These studies will characterize the metabolic, permeability, and membrane structural abnormalities in these RBCs. (3) The cation requirements for amino acid transport will be characterized in human reticulocytes, and the role of cation-amino acid contransport as a determinant of RBC hydration will be evaluated.